Known mechanisms for blood coagulation thrombosis and haemostasis are well described in International Patent Publication WO91/01382 the contents of which are incorporated herein by reference.
It is known from International Patent Publication WO93/01261, Bertina, R. M., Keulemans, B. P. C., Koster, T., et al, "Mutation in blood coagulation factor V associated with resistance to activated protein C", Nature 369, pp. 64 to 67 (1994) and Dahlback et al, "Inherited Thrombophilia: Resistance to activated protein C as a pathogenic factor of venous thromboembolism", Blood 85, pp. 607-614 (1995) that the risk of thrombosis in patients with a mutant factor V molecule known as the Leiden variant, or with activated protein C impairment for some other reason, may be determined by activating the coagulation system in a plasma sample and incubating the sample with activated protein C in what has come to be known as an activated protein C impairment, impedance or resistance test. There are precedents for this test in which impairment of activated protein C has been detected in patients with acquired thrombophilia (Mitchell et al, "Fatal thrombotic disorder associated with an acquired inhibitor of protein C", New England J. Med. 317, pp. 1638 to 1616 (1987) and Amer et al, "Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis", Thromb. Res. 57, pp. 247-1990 (1988).
A substrate conversion reaction rate may be determined by the clotting time or by the time required for the conversion of a chromogenic substrate to a colored product. The conversion rate obtained is compared with values obtained in the absence of activated protein C and also with results for normal plasma samples. If the clotting time is not sufficiently prolonged by activated protein C, it indicates that the individual from which the sample is derived may be at a higher-than-normal risk of thrombosis.